Did Meldonium Help Sharapova?

From the New York Times March 10:

Meldonium is sold under the brand name Mildronate by Grindeks, a company in Latvia, where the drug was invented in the 1970s, and has been one of the country’s major exported products. It is now made by other companies as well.

The compound was originally envisioned as a “growth stimulator for animals and fowl,” according to a United States patent granted in 1984.

Instead, it has been sold in Russia and former states of the Soviet Union mainly to treat conditions, like angina and heart attacks, in which the heart is not getting enough oxygen.

Grindeks said it had not applied for approval of the drug in the United States because that would require costly

Photo by Michael Probst/AP

clinical trials. It would not pay for the company to do that because the patent on the drug has expired, and Grindeks could face generic competition…

Sharapova said she had been prescribed the drug for conditions including a magnesium deficiency, irregular electrocardiograms and prediabetes. Some experts said they did not see how meldonium would necessarily help those conditions (although there are at least two studies in rats showing that the compound might help with diabetes). The F.D.A. has approved many drugs for heart conditions and diabetes.

Meldonium appears to work by inhibiting the synthesis of a substance called carnitine, which the cells in the body need to burn fat to produce energy. But when cells are not getting enough oxygen, they can switch to burning glucose instead of fat. Glucose produces more energy for a given amount of oxygen than fat.

“Glucose is more efficient when you have limited oxygen,” said Dr. William R. Hiatt, a cardiologist and professor at the University of Colorado School of Medicine.

That could explain why the drug would help people whose heart cells were not getting enough oxygen. One randomized controlled trial showed that the use of meldonium increased how long patients with angina, or chest pains from inadequate blood flow to the heart, could ride an exercise bike.

That might also, in theory, suggest why the drug would help athletes. At maximum exertion, their cells might not be getting enough oxygen. Use of the drug might help switch the cells to burning glucose instead.

“In general, if one is involved in short-duration, sprint-type activity, one tends to use glucose because it is more available and it is an efficient way to generate energy quickly,” said Dr. Eric Brass, a professor of medicine at U.C.L.A. who has studied the effects of carnitine.

Still, Brass said it was not clear if that was what was really happening in athletes. “The science behind many of these performance-enhancing compounds is limited, biased and subject to misinterpretation,” he said. Several of the studies on meldonium were done on rats and published only in Russian…

Grindeks said it did not believe meldonium’s use should be banned for athletes. It said the drug worked mainly by reducing damage to cells that can be caused by certain byproducts of carnitine.

Meldonium “is used to prevent death of ischemic cells and not to increase performance of normal cells,” it said in a statement. “Meldonium cannot improve athletic performance, but it can stop tissue damage in the case of ischemia,” which is lack of blood flow to the heart.

Still, one of the drug’s inventors, Ivars Kalvins, told a newspaper in 2009 that the drug had been used to increase the endurance of Soviet troops lugging heavy equipment in Afghanistan. And Grindeks’s website says that in addition to its use for cardiovascular disease, the drug is used “for the improvement of work capacity of healthy people at physical and mental overloads and during rehabilitation period.”